Article
Multidisciplinary Sciences
Peter Nietmann, Kevin Kaub, Andrejus Suchenko, Susanne Stenz, Claas Warnecke, Mohan K. Balasubramanian, Andreas Janshoff
Summary: This study investigates the implications of different actins expressed in epithelial cells for network mechanics and dynamics. The authors find that gamma-actin forms stiffer networks compared to beta-actin, attributed to selective interactions with Mg2+-ions. They also observe that beta-actin networks show more small contraction foci, while gamma-actin networks have fewer but larger foci, indicative of a stronger interaction with myosin motors.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Christopher Tsiros, Emily Punch, Emily Schaffter, Sabrina Apel, Matthew J. Gage
Summary: Titin, the largest muscle protein, plays a crucial role in muscle tension, sarcomeric integrity, and cell signaling. This study demonstrates that the N2A region of Titin binds to F-actin through specific domains, and this binding is length-dependent and calcium-dependent.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Hao Zheng, Zhang-Jun Cheng, Bo Liang, Zhen-Guang Wang, Yuan-Ping Tao, Sheng-Yu Huang, Jun-sheng Ni, Hui-Fen Li, Le Yang, Sheng-Xian Yuan, Jennifer Wu, Takumi Kawaguchi, Hrishikesh Samant, Wei-Ping Zhou, Dai-Min Xiang, Yuan Yang
Summary: Bones are the second most common site of extra-hepatic metastasis in Hepatocellular Carcinoma (HCC), which has limited treatment options and poor prognosis. The key regulators responsible for m6A RNA modification-induced HCC bone metastases (BM) are METTL3 and YTHDF1. The over-expression of ANLN, regulated by m6A epitranscriptomic modification by METTL3 and YTHDF1, is clinically correlated with BM in HCC patients. Inhibition of ANLN m6A modification attenuates HCC BM, suggesting potential therapeutic targets.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2023)
Article
Cell Biology
Jocelyn F. Krey, Chang Liu, Inna A. Belyantseva, Michael Bateschell, Rachel A. Dumont, Jennifer Goldsmith, Paroma Chatterjee, Rachel S. Morrill, Lev M. Fedorov, Sarah Foster, Jinkyung Kim, Alfred L. Nuttall, Sherri M. Jones, Dongseok Choi, Thomas B. Friedman, Anthony J. Ricci, Bo Zhao, Peter G. Barr-Gillespie
Summary: The stereocilia rootlet plays a critical role in protecting vertebrate hair cells from overstimulation. This study demonstrates that the ANKRD24 protein concentrates at the insertion point of the stereocilia, forming a ring and binding with TRIOBP-5 to maintain its distribution. ANKRD24 and TRIOBP-5 together organize the rootlets, enabling long-term auditory resilience.
JOURNAL OF CELL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Keqiang Liu, Lina Lu, Shanshan Chen, Beilin Gu, Hui Cai, Ying Wang, Wei Cai
Summary: This study describes a male infant with LMOD1 mutations presenting pediatric intestinal pseudo-obstruction (PIPO) symptoms but without megacystis and microcolon. The mutations result in significantly reduced LMOD1 protein levels and impair LMOD1-mediated actin nucleation. Molecular modeling shows the structural changes caused by the mutations. These findings provide further evidence of LMOD1 as a pathogenic gene and highlight the critical role of the ABS2 domain in LMOD1-mediated actin nucleation and protein stability.
Article
Multidisciplinary Sciences
Nikolas Hundt, Daniel Cole, Max F. Hantke, Jack J. Miller, Weston B. Struwe, Philipp Kukura
Summary: This study uses mass photometry to investigate the polymerization process of actin and finds that the traditional nucleation-based models cannot explain the observed distribution of actin oligomers. Instead, the key step of filament formation is a slow transition between different states of an actin filament mediated by cation exchange or ATP hydrolysis. These findings have important implications for understanding the mechanism of actin nucleation and studying protein assembly at the molecular level.
Article
Clinical Neurology
Anne Schaenzer, Melanie T. Achleitner, Dietrich Truembach, Laurence Hubert, Arnold Munnich, Barbara Ahlemeyer, Maha M. AlAbdulrahim, Philipp A. Greif, Sebastian Vosberg, Blake Hummer, Rene G. Feichtinger, Johannes A. Mayr, Saskia B. Wortmann, Heidi Aichner, Sabine Rudnik-Schoeneborn, Anna Ruiz, Elisabeth Gabau, Jacobo Perez Sanchez, Sian Ellard, Tessa Homfray, Karen L. Stals, Wolfgang Wurst, Bernd A. Neubauer, Till Acker, Stefan K. Bohlander, Cedric Asensio, Claude Besmond, Fowzan S. Alkuraya, Moenaldeen D. AlSayed, Andreas Hahn, Axel Weber
Summary: Mutations in the HID1 gene were found to cause early infantile encephalopathy with hypopituitarism as the main presentation, expanding the spectrum of syndromic CNS diseases caused by interference with TGN function.
ANNALS OF NEUROLOGY
(2021)
Article
Pediatrics
Luping Chen, Bin Mu, Yalong Li, Fangjin Lu, Ping Mu
Summary: The DRR1-CREB axis plays a crucial role in the differentiation of neuroblastoma cells and is associated with the outcome of neuroblastoma patients.
PEDIATRIC RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Guang-Fei Wang, Qincai Dong, Yu Bai, Jing Gu, Qingping Tao, Junjie Yue, Rui Zhou, Xiayang Niu, Lin Zhu, Caiwei Song, Tong Zheng, Di Wang, Yanwen Jin, Hainan Liu, Cheng Cao, Xuan Liu
Summary: In this study, we found that the assembly and nucleation function of γ-tubulin, the essential component of the γ-tubulin ring complexes (γ TuRCs), are regulated by phosphorylation mediated by the nonreceptor tyrosine kinase c-Abl. This discovery provides a fundamental mechanism for maintaining the function of microtubules in the cytoskeleton.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Pei-Lin Qi, Hao-Ran Zhou, Qiang-Qiang Zhao, Chao Feng, Yong-Qiang Ning, Yin-Na Su, Xue-Wei Cai, Dan-Yang Yuan, Zhao-Chen Zhang, Xiao-Min Su, Shan-Shan Chen, Lin Li, She Chen, Xin-Jian He
Summary: This study identified an autonomous pathway complex (AuPC) that regulates flowering time by suppressing FLC expression through histone modifications. It was also found that one of the AuPC components, SDG26, associates with FLC chromatin and regulates FLC expression and flowering time independently of its histone methyltransferase activity.
NUCLEIC ACIDS RESEARCH
(2022)
Review
Cell Biology
Congbin Pan, Siqi Wang, Chao Liu, Zhanhong Ren
Summary: The heart reacts to pathological stimuli by undergoing cardiac hypertrophy, which can eventually lead to heart failure. However, the molecular mechanisms underlying cardiac hypertrophy are not well understood. Actin, together with actin-binding proteins (ABPs), plays a crucial role in the formation of myofibrils and is involved in the contractile function and morphological changes in cardiomyocytes. Previous studies have shown that abnormal function of ABPs is implicated in cardiac hypertrophy. In this review, we discuss the role of various actin-binding proteins in the development of cardiac hypertrophy, which may have implications for the prevention and treatment of cardiomyopathy.
Article
Medicine, Research & Experimental
Martijn van de Locht, Sandra Donkervoort, Josine M. de Winter, Stefan Conijn, Leon Begthel, Benno Kusters, Payam Mohassel, Ying Hu, Livija Medne, Colin Quinn, Steven A. Moore, A. Reghan Foley, Gwimoon Seo, Darren T. Hwee, Fady Malik, Thomas Irving, Weikang Ma, Henk L. Granzier, Erik-Jan Kamsteeg, Kalyan Immadisetty, Peter Kekenes-Huskey, Jose R. Pinto, Nicol Voermans, Carsten G. Bonnemann, Coen A. C. Ottenheijm
Summary: Pathogenic variants in TNNC2 have been identified to cause congenital muscle disease, leading to disruptions in Ca2+ binding sites and troponin I binding sites which result in reduced force response of sarcomeres. By replacing mutant TnC with wild-type TnC or using the troponin activator tirasemtiv, contractile dysfunction in patients' myofibers can be repaired, providing therapeutic potential for muscle contractility.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Biochemistry & Molecular Biology
Megan R. Radler, Xiaonan Liu, Megan Peng, Brenna Doyle, Kazuhito Toyo-Oka, Elias T. Spiliotis
Summary: Pyramidal neurons, a major cell type of the forebrain, develop their pyramidal morphology and generate neurites through a network of septin filaments. This network balances the activity of lamellipodia and filopodia to promote neuritogenesis. The septin cytoskeleton is critical for the development of pyramidal neurons and provides a key morphogenetic mechanism for neurite formation.
Article
Clinical Neurology
Jin He, Xiao-Xuan Liu, Ming-Ming Ma, Jing-Jing Lin, Jun Fu, Yi-Kun Chen, Guo-Rong Xu, Liu-Qing Xu, Zhi-Fei Fu, Dan Xu, Wen-Feng Chen, Chun-Yan Cao, Yan Shi, Yi-Heng Zeng, Jing Zhang, Xiao-Chun Chen, Ru-Xu Zhang, Ning Wang, Marina Kennerson, Dong-Sheng Fan, Wan-Jin Chen
Summary: This study identified causal missense mutations in the gene encoding seryl-tRNA synthetase 1 (SerRS) that were associated with Charcot-Marie-Tooth (CMT) disease. Whole-exome sequencing and linkage analysis revealed the correlation between these mutations and the clinical phenotype in affected families. Experimental evidence demonstrated that the mutant SerRS proteins had reduced aminoacylation activity and abnormal dimerization, leading to impaired protein synthesis and induction of eIF2 alpha phosphorylation.
ANNALS OF NEUROLOGY
(2023)
Article
Biochemistry & Molecular Biology
Sharifah Albraiki, Oluwatosin Ajiboye, Rachel Sargent, Moriah R. R. Beck
Summary: Palladin is a protein that binds to actin and is specifically upregulated in metastatic cancer cells. It plays a critical role in embryonic development and wound healing. By comparing the 90 kDa isoform of palladin to the isolated actin binding domain, we found key differences in actin binding stoichiometry, polymerization, and interactions with G-actin.
Article
Genetics & Heredity
Ekanem N. Ekure, Ogochukwu Sokunbi, Paul Kruszka, Maximilian Muenke, Adebowale A. Adeyemo
Summary: Hajdu-Cheney syndrome is an ultra-rare genetic disorder characterized by osteoporosis, distinct facial appearance, and joint laxity. This study presents the first reported case of an African child with this syndrome and identifies a previously unreported association with congenital heart disease.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2023)
Review
Biochemistry & Molecular Biology
Joyita Bharati, Praveen N. N. Chander, Pravin C. C. Singhal
Summary: Glomerular parietal epithelial cells (PECs) play crucial roles in both repair and pathogenesis of kidney diseases. Recent studies have shown that microRNA-193a (miR193a) is involved in the modulation of PEC behavior and its role in diseases such as focal segmental glomerulosclerosis (FSGS) and crescentic glomerulonephritis (CrescGN), where PECs exhibit abnormal proliferation. Inhibition of miR193a reduces crescent lesions in a mouse model of CrescGN, while its induction leads to dedifferentiation of podocytes in a mouse model of primary FSGS.
Article
Urology & Nephrology
Layla Fattah, David C. Thomas, Matthew A. Sparks, Samira S. Farouk
Summary: This study utilized the love and breakup letter methodology to evaluate a free open access medical education tool and analyzed the attitudes and needs of learners at different training stages through focus group discussions. The results showed that learners' attitudes and needs varied depending on the training stage, posing challenges in meeting their learning needs.
CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2023)
Article
Urology & Nephrology
Dana M. Larsen, Christy K. Boscardin, Matthew A. Sparks
Summary: This study investigated the frequency, purpose, and type of free open access medical education (FOAMed) usage among nephrology fellows in the US. The results showed that 74% of fellows used FOAMed, and among them, 33% applied the knowledge gained from FOAMed resources in clinical practice. The purposes of FOAMed engagement varied, including accessing academic opinions, answering clinical questions, and staying up to date with the latest information.
CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2023)
Letter
Cardiac & Cardiovascular Systems
Keisuke Okuno, Keiichi Torimoto, Stephanie M. Cicalese, Tomoki Hashimoto, Matthew A. Sparks, Victor Rizzo, Satoru Eguchi
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2023)
Editorial Material
Urology & Nephrology
Jeffrey B. Kopp, Teruhiko Yoshida
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2023)
Editorial Material
Urology & Nephrology
Jeffrey B. B. Kopp, Kenneth Lempert, Kristen Finne
Summary: Access to essential medical care can be compromised by social disruptions, armed conflicts, and natural disasters. Successful response to these events requires prior planning, preparation, and rehearsal involving healthcare systems, professionals, patients, and their support networks. After-action evaluation is necessary to enhance future responses.
NATURE REVIEWS NEPHROLOGY
(2023)
Review
Cell Biology
Stephanie Naas, Mario Schiffer, Johannes Schoedel
Summary: Renal fibrosis is the final stage of kidney diseases and has a significant impact on patients’ quality of life and survival. Factors such as inflammation, metabolic stress, and hypoxia contribute to the progression of renal fibrosis. Hypoxia-inducible factors have both pro- and antifibrotic effects in acute and chronic kidney diseases. Recent advancements in sequencing technologies provide new insights into the cell type-specific effects of hypoxia on the progression of renal fibrosis, particularly in humans.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2023)
Review
Endocrinology & Metabolism
Ayo P. Doumatey, Amy R. Bentley, Rufus Akinyemi, Timothy O. Olanrewaju, Adebowale Adeyemo, Charles Rotimi
Summary: The past two decades have seen a significant increase in cardiometabolic diseases globally, but the prevalence and incidence of these diseases vary across populations. Populations of African descent are among the most affected but least studied. This underrepresentation is a missed opportunity that could worsen health disparities and hinder the equitable implementation of precision medicine.
TRENDS IN ENDOCRINOLOGY AND METABOLISM
(2023)
Article
Urology & Nephrology
Justin P. Van Beusecum, Fitra Rianto, Jade Teakell, Valentina Kon, Matthew A. Sparks, Ewout J. Hoorn, Annet Kirabo, Nirupama Ramkumar
Summary: The kidneys are crucial for maintaining sodium balance in the body by utilizing multiple sodium transporters along the nephron. Imbalances in renal blood flow and glomerular filtration can lead to alterations in sodium transport, resulting in hypertension and Na+-retentive states. This article provides an overview of nephron sodium transport, discusses clinical syndromes and therapeutic agents affecting sodium transporter function, and highlights recent advancements in the field.
ADVANCES IN KIDNEY DISEASE AND HEALTH
(2023)
Article
Urology & Nephrology
Solomiia Savedchuk, Deep Phachu, Mythri Shankar, Matthew A. Sparks, Lisa M. Harrison-Bernard
Summary: The kidney has a unique structure with two capillary beds in series: the glomerular and peritubular capillaries. The glomerular capillary bed is a high-pressure bed responsible for ultrafiltration and sodium/volume homeostasis. The regulation of resistance in the afferent and efferent arterioles, known as glomerular hemodynamics, determines the glomerular filtration rate (GFR) and renal blood flow. Medications targeting glomerular hemodynamics have shown effectiveness in kidney health. This review discusses tubuloglomerular feedback, disease states, and pharmacologic agents that alter glomerular hemodynamics.
ADVANCES IN KIDNEY DISEASE AND HEALTH
(2023)
Meeting Abstract
Urology & Nephrology
Timothy Hopper, Matthew Sparks, John Middleton
AMERICAN JOURNAL OF KIDNEY DISEASES
(2023)
Meeting Abstract
Urology & Nephrology
James Torain, Anjali Muraleedharan, Komal Safdar, Matthew Sparks
AMERICAN JOURNAL OF KIDNEY DISEASES
(2023)
Meeting Abstract
Urology & Nephrology
Benjamin Catanese, Rasha Raslan, Matthew Sparks, Ruediger Lehrich
AMERICAN JOURNAL OF KIDNEY DISEASES
(2023)
Article
Urology & Nephrology
Daniel Edmonston, Matthew Sparks, Sudarshan Rajagopal, Myles Wolf
Summary: Background chronic kidney disease (CKD) worsens the prognosis for individuals with heart failure with preserved ejection fraction (HFpEF). In the RELAX trial, sildenafil decreased eGFR compared with placebo, but its long-term effects on kidney function in HFpEF are unclear. This study analyzed the influence of sildenafil on acute and chronic eGFR slopes in HFpEF patients. The results suggest that sildenafil induced an acute effect on eGFR without affecting the overall eGFR slope after 24 weeks, indicating that early reduction in eGFR after initiating sildenafil treatment does not pose a long-term risk.